ABSTRACT Systems biology is a relatively new discipline used to understand the complex interactions underlying healthy and diseased states of a cell, tissue, or organism, requiring knowledge of networks of processes and molecular and protein interactions within and among cells, organs, and an organism as a whole. Studies of normal development and birth defects are more established classical disciplines. The integration of systems biologic approaches to the study of normal development and inborn errors of development is emerging. Scientists who are versed in both mathematics and biology are needed to address the complexities of development biology by examining the thousands to millions of factors and events that occur simultaneously in a temporospatial and quantitative manner during the lifetime of an organism. Thus, to promote cross-training in these disciplines, we are submitting a competitive renewal application to continue the integrated training program, ?Interdisciplinary Training in Systems and Developmental Biology and Birth Defects? at the Icahn School of Medicine at Mount Sinai in New York City. During the past four years and one month, we successfully built a program that includes 35 faculty members from 8 different departments, 4 institutes, and 4 multidisciplinary training areas (Developmental and Regenerative Biology, Neurosciences, Genetics and Genomics Sciences, and Biophysics and Systems Pharmacology) of the Graduate School of Biological Sciences at Mount Sinai. An outstanding group of educators and scientists with expertise in systems biology, developmental biology or birth defects, including the Directors and members of the External Advisory, Executive Faculty, and Curriculum Committees, provide the leadership, administration, and mentorship for the program. The Curriculum emphasizes the integration of concepts of developmental biology, inborn errors of development, genomics, molecular biology, biochemistry, physiology, pharmacology, quantitative reasoning, computational biology, and bioinformatics. We have created novel courses, journal clubs, and seminar series combining principles of systems biology, developmental biology and birth defects in order to enhance the unique learning experience. The institutional infrastructure for commitment and enhancement of diversity; selection of potential candidates; recruitment; facilities and resources; training in responsible conduct of research and enhancing reproducibility; support for career development; and training program evaluations are already existent for this training program. To date, we have supported 13 PhD or MD/PhD candidates for 1 to 2 years on this training grant; 3 trainees have gone on to receive their individual NIH F30 or 31 awards, and 3 trainees have graduated and are accepted into excellent postdoctoral training programs. Our predoctoral program provides exciting and unique opportunities for study from genomes and proteins to cells, animal models, and humans at the bench and the bedside. The continuation of this innovative training will undoubtedly produce much needed scientists poised at the frontiers of both computational and developmental biology.